CHRONIC ENDOMETRITIS (CE) BY CD138 IN AN INFERTILE POPULATION: A NON-SELECTION STUDY DISCOVERING BASELINE PREVALENCE AND EFFECT ON EARLY EUPLOID EMBRYO IMPLANTATION

ABSTRACT

Objective: The diagnosis and management of CE is debated1-4. Since many patients undergoing assisted reproductive technology (ART) are only tested after treatment failure, definitive management remains imprecise. The objectives of this study were to 1) determine the prevalence of CE in infertility patients and 2) the impact of CE on euploid embryo implantation. Design: Prospective, blinded, non-selection study of patients undergoing IVF/PGT-A. Materials and Methods: All IVF/PGT-A patients cycling between 6/2019 - 3/2020 were eligible. Exclusion criteria were 1) age 42+, 2) embryo banking/not planning ET, 3) planning untested/fresh/mosaic ET. Consented subjects underwent a standardized endometrial biopsy (EMB) at retrieval. EMB results by a single laboratory were blinded until after single euploid ET resulted in 1) +heartbeat, 2) confirmed SAB or 3) negative hCG. Primary outcome was 1) presence/absence of CE, defined as 1+ plasma cell by CD138/section and 2) ongoing pregnancy rate. Secondary outcomes included number of plasma cells/section and stratified pregnancy outcomes. Power analysis for a prevalence of 20%5 with a 95% confidence = 246 subjects. Statistical analyses included Student’s t-test, Fischer’s Exact, logistic regression with p<0.05 considered significant. Results: 104 subjects consented and underwent EMB. Seven withdrew after EMB with 97 eligible for FET. In all biopsied patients, the mean age was 36.1±3.2 years (range 28-41), 66.4% identified as Caucasian, and the most frequent infertility diagnosis was primary/unexplained infertility (42.3%). On 3/17/20, in compliance with ASRM’s COVID recommendations, all IVF/FET cycles and recruitment stopped, at which time 54/97 had undergone FET/unblinding. There were no differences in age (p=0.83), distribution of race/ethnicity (p=0.57) or infertility diagnoses (p=0.77) between transferred and untransferred patients. Due to COVID cycle stop, unblinded biopsies were reviewed for result only (not unblinded), showing 25/104 biopsies (24.0%) positive for CE with plasma cells ranging 1-34. Demographics of transferred patients showed 46 (85.2%) had a programmed ET, 50 (92.6%) with a grade 3-5Bb or higher, and a median time to ET of 56 days. Overall, 39 (72.2%) had an ongoing pregnancy. 20.4% (11/54) had CE with plasma cells ranging 1-14. Subjects with CE had an ongoing pregnancy rate of 63.6% (7/11) that was not significantly different than 74.4% (32/43) in those subjects that were CE negative (p=0.48). Logistic regression showed no difference in ongoing pregnancy when stratified by cycle type, time to ET, lining thickness, embryo day or grade, and plasma cell count. To date, the SAB rate after implantation was similar (2/7 CE positive vs. 1/32 in CE negative, p=0.07). Notably, plasma cell count had an AOR 0.822 (0.668-1.01) and the only 2 SABs seen in patients with CE had plasma cell counts >10. Conclusions: We found a baseline prevalence of roughly 24.0% in ART patients that, to date, did not affect the ongoing pregnancy rate. Further analysis with a larger cohort to examine 1) the SAB rate, 2) alternative definitions of CE, and 3) the impact of COVID are necessary. References 1. Cicinelli, E., Matteo, M., Tinelli, R., Lepara, A., Alfonso, R., Indraccolo, U., Marrocchella, S., Greco, P. & Resta, L. (2015). Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Human Reproduction. 30(2) 323-330. 2. Liu Y, Chen X, Huang J, Wang C, Yu M, Laird S, Li T. Comparison of the prevalence of chronic endometrisias determined by means of different diagnostic methods in women with and without reproductive failure. Fertility and Sterility. 2018;109(5) 832-8329. 3. Bouet P, El Hachem H, Monceau E, Gariepy G, Kadoch I, Sylvestre C. Chronic endometritis in recurrent pregnancy loss and recurrent implantation failure prevalence and role of hysteroscopy and immunohistochemistry in diagnosis. Fertility and Sterility. 2016;105(1) 106-110. 4. Vitagliano A, Saccardi C, Noventa M, Di Spiezo Sardo A, S ccone G, Ciccinelli E, Pizzi S, Andrisani A, Litta PS. Effects of chronic endometritis therapy on in vitro fertilization outcome in women with repeated implantation failure a systematic review and meta-analysis. Fertility and Sterility. 2018;110(1) 103-112e1. 5. Masbou AK, Keefe DL, Fino ME, Hodes-Wertz B, Blakemore JK, Grifo JA. Why do euploid embryos fail to implant? The role of CD138 and chronic endometritis. Current Opinion in Gynecology and Obstetrics. 2019;2(1) 372-378.Â